Manufacture of new pharmaceutical products



Patented May 27, 4930 UNITED STATES em sonumumm, or vonwmxnn, NEAR EL'BERFELD, AND rmrz scnonnornn PATENT. OFFICE AND AUGUST WINGLEB, 'OF ELBERFELD, GERMANY, ASSIGNORS TO WINTHROP cannon. COMPANY, INC-, 01 NEW YORK, N. Y., A CORPORATION OF NEW YORK MANUFACTURE OF NEW PHARMACEUTICAL PRODUCTS Io Drawing. Application filed December 16, 1927, Serial No'.240,621, and in Germany December 20, 1928.

The present invention relates to compounds oi the general formula:

- on a I wherein the acridine nucleus may be further a substituted and wherein R represents hydrogen, an alkyl group, and ammoalkyl group or any other monovalent substituent, and R represents an alkylene residue which is substltuted by a heterocyclic residue containing nitrogen 'or by a hydro-aromatic residue which is substituted by a primary, secondary or tertiary amino group, and to a process of preparing these compounds.

We have found that these compounds are exceedingly valuable and effective new remedies for use in therapy. 7

lhe manufacture of our new compounds can be efiected in several ways, for instance, by reacting upon a compound of the general formula wherein the acridine nucleus may be further substituted and wherein R represents hydrogen, an alkyl group, an aminoalkyl group or any other monovalent substituent with a compound of the general formula:

und; in the last case the phthalic acid is to t? split off subsequently.

One molecule =t-amino-acridi1'1'e and one 1 molecule a-piperidylethylchloride (hydroyellow, Viscous oil, curdling at low temperature. Its hydrochloric salt is easily soluble. in water with a wine-red color.

Ewa/mple 2 ,ou O mn NH HLCHLN ()nemolecule of 4-amino-acridine and one molecule of pyrolidylethyl-chloride (hydrochloric acid salt) are melted together for 8 hours at a temperature of 110120 C. while stirrlng. The reaction mass is worked up as described in Example 1. The new compound is a viscous yellow oil, boiling at 215220 C. under a pressure ofl mm. Its hydrochloric salt is easily soluble in water with a wine-red color.

Ewmnple 3 brompiperidine (hydrobromic salt) are melted together for 12 hours at a temperature I of 15 160 C. while stirring. Thereaction mass is dissolved in diluted hydrochloric acid v and filtered from a dark mass insoluble in gen, an alkyl group, an amino-a diluted hydrochloric acid. Then a solution of sodium acetate is added,'ti]l the free hydrochloric acid has disappeared. 5 The residue of the unchanged 4-amino-acridine precipitates andis separated by ether. From the aqueous solution our new compound is precipitatedjb caustic soda lye. By watersteam-distillatlon easily volatile amines ing formula:

I on Qlnfl NH BIO cm A0 N-C O s-43 mo H.

We claim I 1. As new products the compounds of the general formula:

wherein the acridine nucleus may be further substituted and wherein R represents hydroy group or any other monovalent substituent and R represents an alkylene residue which is substituted by a heterocyclic residue containing nitrogen by a hydro-aromatic residue which is substituted by a primary, secondary or".

tertiary amino group, being valuable therapeutical substances.

2. As new productsthe compounds of the general formula:

wherein. the acridine nucleus may be further substituted and wherein R represents hydrogen, 'an alkyl group, an amino-alkyl group or any other monovalent substituent and R represents an alkylene residue which is substituted by a heterocychc residue containing nitrogen or by a hydro-aromatic residue otash and with ether, con-.

which is substituted by a primary, secondary or tertiary amino group, being valuable therapeutical substances.

- As new products general formula:

/U N H R which is substituted by a heterocyclic residue containing nitrogen, being valuable therapeutical substances.

4. As new products the compounds ofthe general formula:

Goo A.

wherein R represents an ethylene residue which is substituted by a heterocyclic residue containing nitrogen, being valuable therapeuticalsubstances. I

5. As a new product the compound of the general formula:

v v I) N NE CHI-CH:

being a golden-yellow oil, boiling at a temperature of 220-2259 0. under a pressure of 1 mm., curdling at a lower temperature, its hydrochloric salt being easily soluble in water with a wine-red color, \and being a valuable pharmaceutical substance.

6. The, process which comprises reacting upon a compound of the general formula:

wherein the acridine residue may be further substituted and whereinR represents hydrogen, an alkyl group, an aminoalkyl group or any other-monovalent residue with a com-v pound of the general formula y.R wherein y represents halogen and R represents an the compounds of the l wherein R represents an alkylene residue alkylene residue which is substituted by a heterocyclic residue containing nitrogen or a hydro-aromatic residue which is substituted by primary, secondary or tertiary amino group. t

7. The recess, of roducin a com um]. of the for inula: g p

CH g qn H CHr-CH Ha-CHz-N OH! 1 CHa-CH r t which process comprises reacting upon- 4-amino-acridine with the hydrochloric salt of a-piperidyl-ethylchloride.

In testimony whereof we have hereunto set our hands. WERNER SQHULLMANN.

FRITZ SOHONHOFER. AUGUST WINGLER.

so I 

